ACTA ENDOCRINOLOGICA (BUC)

Phenylketonuria (PKU) is the most frequent inherited amino acid metabolic disorder, and it may also be treated by dietary means. The determination of phenylalanine (Phe) levels in the blood plasma is important not only in early diagnostic, but also in monitoring the treatment of PKU. Purpose. The aim of our work was to develop a simple, sensitive and highly accurate procedure to determine the plasma concentration of Phe. Procedure. The measurement of plasma Phe concentration involves two steps: a) separation of plasma (from the blood taken on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex-50X8 and evaporation of the eluate in vacuum at 40˚C), and b) determination of Phe concentration in the solution of amino acids by HPLC. This analysis was performed using a Dionex Ultimate 3000 instrument equipped with a Ultimate 3000 diode array detector (DAD). The values of Phe concentration in the plasma of several patients were calculated using a calibration curve made with standards of Phe (dilutions of a stock solution of 50 mg/ dL). The measurements in duplicate (plasma Phe) or a greater number of samples from the same concentration of standards of Phe showed extremely small sample to sample differences. Concentrations as low as 0.2 mg/dL could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and highly accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentration of Phe in patients with PKU.

Objective. We aimed to investigate the potential relationship between plasma alarin levels and type 2 diabetes mellitus (T2DM). Patients and Method. We included 154 participants, divided into four groups in a cross-sectional study design. The first group includes patients with T2DM without complications (n=30), the second group patients with T2DM with microvascular complications (T2DMnoC n=32), the third group patients with T2DM with macrovascular complications, T2DM-MV (n=32) and the last group is the healthy control group (n=60). Results. In our study 94 patients were diabetic; 47 females and 47 males. The control group consists of 60 people, 30 women and 30 men. It was found that these had a significant (p>0.05) variation in serum alarin levels among the T2DM (T2DM-noC=3.1±0.7 ng/mL T2DMmV=2.8±0.4 ng/mL, T2DM-MV= 3.6±0.4 ng/mL) versus control group (15.6±2.6). We failed to find a significant variation of serum alarin levels (p>0.05) between T2DM subgroups. Serum alarin levels were significantly higher among control patients (p<0.05). There was no difference between diabetic sub-groups. Conclusion. We concluded that serum alarin levels in patients with T2DM are lower than in normal people. Further studies are needed to investigate the possible prognostic value of alarin in clinical practice in T2DM.

Introduction. Non-diagnostic (ND) fine needle aspiration biopsy (FNAB) results are problematic for clinicians who want to accurately diagnose malignancy and avoid unnecessary thyroidectomies. In this study, we aimed to investigate the incidence of malignancy in nodules whose first FNAB result was ND, and ultrasonography (USG) findings affecting malignancy and the effectiveness of repetitive biopsies. Patients and Method. In our clinic, 156 consecutive nodules whose first FNAB were ND according to the Bethesda system and underwent thyroidectomy between 1 January 2011 and 1 January 2018, directly or after repeated biopsies, were retrospectively analyzed. Results. Malignancy was detected in 44 (28%) of 156 nodules that were ND in the first FNAB. Twenty-two (31%) of 72 nodules that underwent FNAB for the second time resulted in ND again. The malignancy rate of nodules with two consecutive ND results was 23%. Of the USG features, a significant correlation was found between malignancy and solid nodule structure (p<0.001), microcalcification (p=0.025), cervical lymphadenopathy (LAP) (p=0.004) and medium-high risk USG pattern (p=0.002). In multivariate analysis, only the solid nodule structure (p<0.002) and the presence of cervical LAP (p=0.013) resulted as independent predictive factors. Conclusion. Diagnostic thyroidectomy is an effective method for reaching the diagnosis in selected patients considering the USG findings.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. Aim. To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. Design. The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). Subjects and Methods. Exclusion criteria: age <40/ or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological subregion where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. Results. A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study. The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6- 6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/ obesity and smoking were associated with high CVR categories. Conclusion. Romania is one of the countries with high CVR, requiring CVD prevention measures.

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.

Background. Multiple endocrine neoplasia type 2B (MEN 2B) is a rare hereditary syndrome caused mainly by Met918Thr germline RET mutation and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and typical phenotypic features. MEN 2B cases previously reported in the literature have variable clinical course. Objectives. We aimed to discuss the characteristics of four MEN 2B cases with unusual presentations,clinical course and review the recent clinical data on MEN2B Results. All patients had de novo M918T mutation and no family history. The mean age of patients was 38.2 years (27-56). Two patients had typical phenotypic features of MEN 2B; the other two patients had no striking phenotypic features. First detected MEN 2B component was MTC in two, intestinal ganglioneuromatosis in one, and PHEO in one of the cases. Bilateral PHEO was detected in all four cases. Conclusions. MEN 2B is a complex syndrome characterized by wide phenotypic variability and different clinical outcomes. To diagnose sporadic MEN 2B cases, genetic testing should be performed in all cases with suspicious clinical features. Although early diagnosis is the main factor that increases life expectancy, some MEN 2B patients with late diagnosis may exhibit a mild clinical course and better prognosis than expected, with effective treatment.

Context. Suicide is a global public health issue. Bipolar disorder (BPD) has the highest suicide risk among individuals suffering from mental disorders. Serotoninergic dysfunctions have been linked to suicidal behaviour and platelet serotonin is recognised as a reliable index for the presynaptic serotonin activity. Objective. Our aim was to assess whether alterations occur in platelet serotonin concentrations in BPD type I in respect to suicide attempters compared with nonattempters. Design. This was a cross-sectional, observational study. Subjects and Methods. Plasma platelet serotonin concentrations were measured using ELISA technique in 71 BPD I patients. The participants were assigned into 3 groups (non-attempters, low lethality and high lethality suicide attempters), according to the Columbia-Suicide Severity Rating Scale. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire designed specifically for this research. Results. Our study showed significant lower levels of platelet serotonin in suicide attempters compared with non-attempters (p = 0.030) and in high-lethality attempters compared with low-lethality attempters (p = 0.015). The study recorded a higher number of total lifetime and lifetime depressive episodes for suicide attempters with BPD I. Conclusions. Our results subscribe to the importance of platelet serotonin as a reliable biomarker in suicide risk assessment.

Objective. This study aimed to evaluate the utility of C-peptide levels in the differentiation of monogenic forms of diabetes from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in clinical practice. Subjects and Methods. A total of 104 patients aged >16 who visited the Dicle University’s Faculty of Medicine between April 2011 and December 2020 and were diagnosed with monogenic diabetes by genetic analysis or with T1DM and T2DM were randomly selected for retrospective evaluation. The C-peptide levels of these patients at the time of diagnosis of diabetes were compared. Results. Of the 104 patients, 24 (23%) were diagnosed with maturity-onset diabetes of the young (MODY), 40 (38.5%) with T1DM, and 40 (38.5%) with T2DM. Median C-peptide levels (ng/mL) (interquartile range) were 1.78 (1.24–2.88) in MODY group, 0.86 (0.34– 1.22) in T1DM group, and 2.38 (1.58–4.27) in T2DM group. Conclusions. There was a difference in C-peptide levels between MODY and T1DM groups but not between MODY and T2DM groups. As per clinical evaluations, although C-peptide levels of patients with MODY are similar to those of patients with T2DM patients, the possibility of C-peptide levels being similar to those required for T1DM diagnosis should also be considered.

Introduction. Patients with breast cancer are treated after surgery by radiation and\r\nchemotherapy, potentially nephrotoxic. Patients with tumor estrogen-positive receptors are then\r\ntreated with Tamoxifen with a possible renoprotective effect. Aim. To assess the effects of\r\nradiation and chemotherapy and of Tamoxifen on renal function in patients with breast cancer.\r\nPatients and Methods. We undertook a retrospective observational study on 76 breast\r\ncancer patients during 2002-2006. Depending on the estrogen receptor status of the tumour\r\nthey were divided into group A (estrogen positive) with 50 patients, mean age: 57.64?9.34,\r\ntreated with Tamoxifen and group B (estrogen negative), 26 patients, mean age: 50?9.83\r\nwho did not receive Tamoxifen. Both groups underwent surgical tumor resection, radiation\r\nand chemotherapy. The TNM status of the tumours was similar in both groups. (2/3 stages\r\nI and II and 1/3 stages III and IV). We followed up the GFR (MDRD 4) before radiation and\r\nchemotherapy and after this treatment. Thereafter, we followed up the GFR in group A at 1,\r\n2 and 3 years of Tamoxifen and in group B at 1, 2 and 3 years of radiation and\r\nchemotherapy. Statistical analysis was performed using OpenEpi 2.3. software.\r\nResults. In group A the GFR declined not significantly after radiation and chemotherapy\r\nand at 1 year of Tamoxifen. At 2 ys of Tamoxifen, in the 18 surviving patients the GFR\r\nincreased from 61.13?17.53 mL/min to 66.56?16.3 mL/min (p=0.009). At 3 y of Tamoxifen,\r\nthe 12 surviving patients showed a preservation of the GFR. In group B the GFR declined from\r\n88.14?14.63 mL/min (baseline) to 80.01?20.62 mL/min (p=0.0001) after radiation and\r\nchemotherapy. At 1 y after radiation and chemotherapy the GFR declined to 78.21?17.65\r\nmL/min (p<0.001). At 2 y after radiation and chemotherapy in the 18 surviving patients the\r\nGFR declined to 70.94?13.39 mL/min (p<0.001 as compared to baseline). At 3 y in the 8\r\nsurviving patients the GFR declined to 61.36?9.17 mL/min (p=0.001 as compared to baseline).\r\nConclusions. Patients undergoing treatment with Tamoxifen (group A) showed a\r\npreservation of their renal function. In patients undergoing radiation and chemotherapy\r\nalone (group B) we noticed a decline of the Glomerular Filtration Rate.

Context. Thyroid hormones have metabolic effects such as relationship between hypothyroidism and atherosclerosis. Objective. Evaluate the effects of hypothyroidism on Non-Alcoholic Fatty Liver Disease and atherosclerosis by using AIP, APRI score, FIB-4 indices. Material and Methods. 1370 patients with hypothyroidism who applied to the Endocrinology and Metabolism outpatient clinic between 01.01.2017-30.12.2021 were included the study. Pregnants, patients with a history of thyroid carcinoma, cardiovascular and liver diseases were excluded. TSH, fT4, Anti TPO, Anti TG, thrombocyte, ALT, AST, HDL, Triglyceride values of the cases were analyzed and atherogenic index of plasma (AIP), AST to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) indices were calculated. Results. 1170 (85.4%) of the cases were female.The age of those who had high risk of AIP was found to be higher than those with low and moderate risk (p=0.001; p=0.003; p<0.01). The ages of those who had low-risk FIB-4 Index were found to be lower than those with moderate risk and high risk (p=0.001; p=0.001; p<0.01). A positive relationship was detected between APRI and FIB-4 (r=0.681; p=0.001; p<0.01).AIP increased as TSH increased in hypothyroid patients. No significant correlations were detected between TSH, APRI, and the FIB-4 Index. No significant differences were detected between AIP, APRI, FIB-4, and thyroid autoantibodies. Conclusion. In hypothyroid patients, the AIP index increased with age and the increase in TSH. A strong relationship was detected between AIP and TSH . For this reason, we think that keeping TSH within the normal range with regular follow-ups and treatment in patients with hypothyroidism will reduce the risk of atherosclerosis.